Nanoparticle-delivery system enhanced the improvement and recovery in toxicity-induced acute hepatic failure

J Chin Med Assoc. 2019 May;82(5):363-367. doi: 10.1097/JCMA.0000000000000066.

Abstract

Background: The major curative remedy for advanced liver failure is hepatic transplantation. However, the conventional medicine still shows the limitations and obstacles for liver regeneration. Importantly, it is unclear whether we can get a rapid and high efficacy platform to facilitate to reprogram hepatic capability. The main work of this study was to develop a platform for a nanomedicine-based gene-delivery platform of novel nanoparticles (NNPs) to efficiently facilitate the liver function recovery.

Methods: In this study, we studied the feasibility and efficiency of NNP and produced the multiple abilities of NNPs for a potential platform of gene transduction. We showed that NNPs played an important role in hepatic protection. The cytoprotective effects of NNPs in toxic-hepatic cells were investigated and evaluated by cell viability, reactive oxygen species production, in vitro cell abilities, and in vivo animal studies.

Results: We demonstrated that NNPs possess the abilities to protect the cell after toxic-stress both in vitro and in vivo. Under the stress condition, our result showed that cell viabilities can be improved by NNP-carried hepatocyte nuclear factor 3 (HNF3) gene (NNP-HNF3), which is a famous hepatic transcriptional factor and regenerative marker to modulate essential molecular pathways activating various hepatic-specific markers. Importantly, compared to control and NNP-control, NNP-HNF3 exhibited the cytoprotective effects that prevented toxic-induced oxidative stress and cell damage in vitro as well as in vivo. Notably, our data showed that NNP-HNF3 treatment may improve toxic-induced hepatic encephalopathy.

Conclusion: Herein, we demonstrated that novel nanoparticle, such as NNP-HNF3, serves as a key regulator for protecting the damaged hepatic cell and the bioproduct-based source for the new therapeutics of hepatic failure.

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury / therapy*
  • Cytoprotection
  • Gene Transfer Techniques*
  • Hep G2 Cells
  • Hepatocyte Nuclear Factor 3-alpha / genetics*
  • Humans
  • Liver Failure, Acute / therapy*
  • Male
  • Mice
  • Nanoparticles / administration & dosage*
  • Oxidative Stress

Substances

  • FOXA1 protein, human
  • Hepatocyte Nuclear Factor 3-alpha